Investigation of hemophagocytic lymphohistiocytosis in severe sepsis patients

Halaçlı, Burçin; Ünver, Neşe; Halaçlı, Sevil Oskay; Canpınar, Hande; Ersoy, Ebru; Öcal, Serpil; Güç, Dicle; Büyükaşık, Yahya; Topeli, Arzu

doi:10.1016/j.jcrc.2016.04.034

Cited by 18 publications

(17 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A few studies have focused on the role of acute infectious triggers in HLH survival, mainly in pediatric patients, 20 , 21 but also in adults treated with biological agents. 22 However, some descriptive studies have reported higher mortality rates in patients presenting with bacterial infections 13 , 23 , 24 or co-infections. 21 , 25 Our study reports, for the first time, that both the variety and number of infectious triggers implicated in HLH have a considerable influence on survival using time-to-event statistical models; the best survival curve was found for patients with parasitic/fungal infections, followed by those with viral infections, whereas the worst survival curves were for those with bacterial infections and multiple microbiological infections (of whom 71% also had bacterial infections in association with other microorganisms).…”

Section: Discussionmentioning

confidence: 99%

Prognostic Factors of Death in 151 Adults With Hemophagocytic Syndrome: Etiopathogenically Driven Analysis

Brito-Zerón¹,

Kostov

Moral-Moral

et al. 2018

Mayo Clinic Proceedings: Innovations, Quality & Outcomes

View full text Add to dashboard Cite

ObjectiveTo characterize the etiologies and clinical features at diagnosis of patients with hemophagocytic lymphohistiocytosis (HLH) and correlate these baseline features with survival using an etiopathogenically guided multivariable model.Patients and MethodsThe Spanish Group of Autoimmune Diseases HLH Study Group, formed in 2013, is aimed at collecting adult patients with HLH diagnosed in internal medicine departments between January 3, 2013, and October 28, 2017.ResultsThe cohort consisted of 151 patients (91 men; mean age, 51.4 years). After a mean follow-up of 17 months (range, 1-142 months), 80 patients died. Time-to-event analyses for death identified a worse survival curve for patients with neoplasia (P<.001), mixed microbiological infections (P=.02), and more than 1 infection (P=.01) and glucocorticoid monotherapy (P=.02). According to univariate analyses, platelets of less than 100,000/mm3 (hazard ratio [HR], 3.39; 95% CI, 1.37-8.40), leukopenia (HR, 1.81; 95% CI, 1.01-3.23), severe hyponatremia (HR, 1.61; 95% CI, 1.02-2.54), disseminated intravascular coagulation (HR, 1.87; 95% CI, 1.05-3.34), bacterial infection (HR, 1.99; 95% CI, 1.09-3.63), mixed microbiological infections (HR, 3.42; 95% CI, 1.38-8.46), and 2 or more infectious triggers (HR, 2.95; 95% CI, 1.43-6.08) were significantly associated with death. In contrast, peripheral adenopathies (HR, 0.63; 95% CI, 0.40-0.98) and the immunosuppressive drug/intravenous immunoglobulin/biological therapies (HR, 0.44; 95% CI, 0.20-0.96) were protective against all-cause mortality. Multivariable Cox proportional hazards regression analysis identified 2 or more infectious triggers (HR, 3.14; 95% CI, 1.28-7.68) as the only variable independently associated with death.ConclusionThe mortality rate of adult patients diagnosed with HLH exceeds 50%. Infection with more than 1 microbiological agent was the only independent variable associated with mortality irrespective of the underlying disease, epidemiological profile, clinical presentation, and therapeutic management.

show abstract

Section: Discussionmentioning

confidence: 99%

Prognostic Factors of Death in 151 Adults With Hemophagocytic Syndrome: Etiopathogenically Driven Analysis

Brito-Zerón¹,

Kostov

Moral-Moral

et al. 2018

Mayo Clinic Proceedings: Innovations, Quality & Outcomes

View full text Add to dashboard Cite

show abstract

“…9 Although classically described in children, septic hyperferritinemic adults are also at risk of poor outcome. 9,10 Additionally, while overall, interleukin-1β receptor antagonist (IL1RA) therapy was ineffective for septic shock, post-hoc subgroup analysis showed that patients with MAS features experienced a 50% relative risk reduction for mortality when treated with IL1RA. 11,12 As the hyperferritinemic sepsis phenotype overlaps with other inherited immunologic disorders, including hemophagocytic lymphohistiocytosis (HLH), Cryopyrin Associated Periodic Syndromes (CAPS), Familial Mediterranean Fever, and atypical Hemolytic Uremic Syndrome (aHUS), we hypothesized that known pathogenic disease variants for these disorders would be identified in individuals with this sepsis phenotype.…”

Section: Introductionmentioning

confidence: 99%

Adults with septic shock and extreme hyperferritinemia exhibit pathogenic immune variation

Kernan

Ghaloul‐Gonzalez

Shakoory³

et al. 2018

Genes Immun

View full text Add to dashboard Cite

Post-hoc subgroup analysis of the negative trial of interleukin-1β receptor antagonist (IL1RA) for septic shock suggested that patients with features of macrophage activation syndrome (MAS) experienced a 50% relative risk reduction for mortality with treatment. Here we seek a genetic basis for this differential response. From 1341 patients enrolled in the ProCESS trial of early goal directed therapy for septic shock, we selected 6 patients with MAS features and the highest ferritin, for whole exome sequencing (mean 24,030.7 ηg/ml, ±SEM 7,411.1). In total 11 rare (minor allele frequency <5%) pathogenic or likely pathogenic variants causal for the monogenic disorders of Familial Hemophagocytic Lymphohistiocytosis, atypical Hemolytic Uremic Syndrome, Familial Mediterranean Fever, and Cryopyrin-associated Periodic Fever were identified. In these conditions, seven of the identified variants are currently targeted with IL1RA and four with anti-C5 antibody. Gene-targeted precision medicine may benefit this subgroup of patients with septic shock and pathogenic immune variation.

show abstract

“…Обнаружено также, что при ВГФС частота спленомегалии, уровень триглицеридов, ферритина, аланин-(АлАТ) и аспартатаминотрансферазы (АсАТ) статистически значимо выше, чем при сепсисе, а уровень гликозилированного ферритина (%ГФ), фибриногена, лейкоцитов, нейтрофилов и тромбоцитов -ниже. Приведены медианы (1-3-й квартиль) значений в группах пациентов с ВГФС и сепсисом соответственно: триглицериды (ммоль/л) -3,1 (2,3-3,8) и 1,5 (0,8-2,7), общий ферритин (нг/мл) -7170 (3159,2-12551,0) и 1274 (559,0-3041,5), %ГФ -26,5 (16,3) и 54,5 (37,8), фибриноген (г/л) -2,8 (1,4-4,4) и 5,3 (2,8), АлАТ (МЕ/л) -50 (20-102) и 30 (15,5), АсАТ (МЕ/л) -66 (40,6) и 36 (24,0), лейкоциты (×10 9 /л) -3,7 (2,1-5,5) и 8,9 (6,(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)5), тромбоциты (×10 9 /л) -56 (25,2-93,5) и 157 (97-308). По данным ROC-анализа, площадь под кривой для уровня нейтрофилов составила 0,88, общего ферритина, %ГФ, лейкоцитов и тромбоцитов -0,85, триглицеридов -0,74, фибриногена -0,71, натрия -0,65, АлАТ и АсАТ -0,61.…”

Section: клиническая онкогематологияunclassified

“…Гиперцитокинемия часто развивается на фоне онкогематологических заболеваний, а также любого воспаления [5,[35][36][37][38][39]. Нам не удалось выявить различия по уровням цитокинов, а также концентрации поверхностных молекул CD25 и CD163 при ВГФС и сепсисе.…”

Section: рис 3 корреляционный анализ концентрации общего и гликозилunclassified

“…Так, по данным крупных исследований, сепсис в отсутствие иммунодефицита может иметь черты ВГФС у 4,3 % больных. Возможно, данная группа пациентов нуждается не только в противоинфекционной терапии, поскольку она зачастую оказывается безуспешной [4][5][6]. При исходном нарушении иммунитета распространенность ВГФС выше [7].…”

Section: Introductionunclassified

See 1 more Smart Citation

Clinical and Laboratory Characteristics and Differential Diagnosis between Secondary Hemophagocytic Syndrome and Sepsis

Потапенко¹,

Первакова²,

Титов³

et al. 2019

Клиническая онкогематология

View full text Add to dashboard Cite

Актуальность. Вторичный гемофагоцитарный синдром (ВГФС) и сепсис при всей схожести клинических проявлений и лабораторных параметров принципиально различаются по применяемым при этих заболеваниях методам лечения. При ВГФС лечение направлено на достижение иммуносупрессии, а при сепсисе проводится противоинфекционная терапия. Для выбора правильной лечебной тактики необходима быстрая дифференциальная диагностика между заболеваниями. Цель. Поиск и анализ критериев дифференциальной диагностики ВГФС и сепсиса. Материалы и методы. Проанализированы данные 102 пациентов: 55-с ВГФС (медиана возраста 60 лет, диапазон 18-81 год) и 47-с сепсисом (медиана возраста 60 лет, диапазон 18-89 лет). Диагноз ВГФС установлен на основании критериев HLH-2004 и H-Score. Сепсис верифицирован при документированном очаге

show abstract

Investigation of hemophagocytic lymphohistiocytosis in severe sepsis patients

Cited by 18 publications

References 28 publications

Prognostic Factors of Death in 151 Adults With Hemophagocytic Syndrome: Etiopathogenically Driven Analysis

Prognostic Factors of Death in 151 Adults With Hemophagocytic Syndrome: Etiopathogenically Driven Analysis

Adults with septic shock and extreme hyperferritinemia exhibit pathogenic immune variation

Clinical and Laboratory Characteristics and Differential Diagnosis between Secondary Hemophagocytic Syndrome and Sepsis

Contact Info

Product

Resources

About